Human Natural Antibodies Recognizing Glycan Galβ1-3GlcNAc (LeC) - Archive ouverte HAL Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2020

Human Natural Antibodies Recognizing Glycan Galβ1-3GlcNAc (LeC)

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Abstract

The level of human natural antibodies of immunoglobulin M isotype against LeC in patients with breast cancer is lower than in healthy women. The epitope specificity of these antibodies has been characterized using a printed glycan array and enzyme-linked immunosorbent assay (ELISA), the antibodies being isolated from donors' blood using LeC-Sepharose (LeC is Galβ1-3GlcNAcβ). The isolated antibodies recognize the disaccharide but do not bind to glycans terminated with LeC, which implies the impossibility of binding to regular glycoproteins of non-malignant cells. The avidity (as dissociation constant value) of antibodies probed with a multivalent disaccharide is 10-9 M; the nanomolar level indicates that the concentration is sufficient for physiological binding to the cognate antigen. Testing of several breast cancer cell lines showed the strongest binding to ZR 75-1. Interestingly, only 7% of the cells were positive in a monolayer with a low density, increasing up to 96% at highest density. The enhanced interaction (instead of the expected inhibition) of antibodies with ZR 75-1 cells in the presence of Galβ1-3GlcNAcβ disaccharide, indicates that the target epitope of anti-LeC antibodies is a molecular pattern with a carbohydrate constituent rather than a glycan.
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Dates and versions

inserm-02948773 , version 1 (25-09-2020)

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Kira Dobrochaeva, Nailya Khasbiullina, Nadezhda Shilova, Nadezhda Antipova, Polina Obukhova, et al.. Human Natural Antibodies Recognizing Glycan Galβ1-3GlcNAc (LeC). International Journal of Molecular Sciences, 2020, 21 (18), pp.6511. ⟨10.3390/ijms21186511⟩. ⟨inserm-02948773⟩
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